In peritoneal dialysis, access to the peritoneal cavity is conventionally accomplished either by using a disposable rigid catheter, or, if repeated dialysis is anticipated, by use of a flexible silicon rubber catheter equipped with a Dacron (polyethylene terephthalate) velour cuff (to permit the formation of bacteria-tight seals between the catheter and the abdominal wall). With the catheter in place, sterile, pyrogen-free dialysis fluid is introduced in 250 ml to 3000 ml (milliliter) aliquots, allowed to equilibrate (dwell), and is subsequently drained and discarded.
In the case of patients being treated with peritoneal dialysis for renal failure, urea and creatinine are principally cleared from whole blood during dialysis. However, dialysis is also used in removing toxins or poisons or life-threatening excesses of total body water in the absence of renal failure when renal excretion of such substances is inadequate or compromised by prerenal factors.
It has been estimated that substantial amounts of the dialysate in the peritoneal cavity are removed therefrom by lymphatic circulation. The dialysate so removed is known to be drained from the peritoneal cavity through lymphatic micropores or stomata. Not only does this drainage undesirably reduce the ultrafiltration rate of substances, such as urea and creatinine from whole blood, but also this drainage loss leads to unwanted side effects, such as hyperglycemia.
Apart from peritoneal dialysis, this drainage loss reduces the efficiency of pharmaceutical agents placed within the peritoneal cavity. In the case of drugs with a low therapeutic ratio, it was heretofore not possible to administer such through the peritoneal cavity because of lymphatic drainage even though such administration would otherwise be beneficial for treatments of, or within, the peritoneal cavity, such as with certain antibiotics, and the like. It would be desirable in the art of pharmacology to have, for purposes of pharmaceutical agent administration in the peritoneal cavity, a lymphatic blocking substance which slowly releases material into the vascular system from the peritoneal cavity. For example, a drug might be associated with a particle which is adapted to slowly biodegrade and/or bioerode in a regulated or predictable fashion, thereby controllably releasing the drug so that it can accomplish its function, such as treating interstitial infection, and the like.
In an effort to block or retard lymphatic drainage from the peritoneal cavity, various drugs have heretofore been tried, such as neostigmine, for example. Such trials have been, so far as now known, impractical or ineffective. In the case of neostigmine, undesirable systemic absorption and unwanted side effects have been observed. So far as now known, no previous means was heretofore known by which lymphatic drainage from the peritoneum could be blocked or reduced without evident undesirable side effects.
Peritoneal lymphatic blockade is believed to be desirable principally for purposes of increasing the dwell-time of substances in the peritoneal cavity which are normally cleared by this system. Such a blockade would presumably improve the quality and efficiency of peritoneal dialysis. Apart from dialysis, it is believed to be possible and desirable to administer pharmaceutical agents through the peritoneal cavity in combination with a suitable blocking agent, or to implant in the peritoneal cavity a biologically active body, such as a synthetic organ (e.g., a pancreas), or the like, in combination with a suitable lymphatic blocking agent, in order to prolong the desired duration of pharmacological action within the mammalian body.
The art needs a new and effective technique and associated means for accomplishing lymphatic blockade of the peritoneum via the peritoneal cavity.